title: Methionine diet-induced hyperhomocysteinemia accelerates cerebral aneurysm formation in rats.
abstract: OBJECTIVE
  The pathophysiology of cerebral aneurysms (CA) is linked to chronic inflammation. Endothelial damage is one of the first changes in CA walls resulted from inflammation. It has been shown that increase in plasma homocysteine (Hcy) impairs vascular endothelium and correlates with the development of atherosclerosis. However, the effect of hyperhomocysteinemia (HHcy) on the formation of cerebral aneurysm remains unknown.
  
  
  METHODS
  Male Sprague-Dawley rats examined for developing cerebral aneurysms after surgical induction in the presence and absence of hypercysteinemia induced by a high L-methionine diet (1 g/kg/d). Aneurysms developed at the anterior cerebral-olfactory artery bifurcation were classified as 4 stages from no abnormality to saccular aneurysm. Plasma homocysteine levels and expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2), and MMP-9 in aneurysmal walls was examined and correlated with CA formation 3 months after surgery.
  
  
  RESULTS
  Methionine diet significantly increased plasma homocysteine levels, accelerates CA formation after ligation of the left common carotid artery. Expression of VEGF, iNOS, MMP-2, and MMP-9 in aneurysmal walls was also increased by methionine treatment.
  
  
  CONCLUSIONS
  Hyperhomocysteinemia accelerates cerebral aneurysm formation, potentially through differential effects on expression of molecules critical for vascular wall modeling in a rat model.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin 300052 PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Wei
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Dong
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004032:Diet / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000150:complications*; D007249:Inflammation / Q000378:metabolism; D002532:Intracranial Aneurysm / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008715:Methionine / Q000009:adverse effects*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D042461:Vascular Endothelial Growth Factor A; D008715:Methionine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9